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Biotage® MP-Cyanoborohydride is a macroporous polymer supported cyanoborohydride. It is a versatile reducing agent for the reductive amination of carbonyl compounds and reduction of imines. The reaction work-up protocol is greatly simplified by using the solid supported reagent. Specifically, compared with the small molecule sodium cyanoborohydride, it is reported that toxic cyanide is not released on reaction workup and therefore does not contaminate the product or pose a danger towards the user.

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Biotage® MP-Cyanoborohydride is a macroporous polymer-supported cyanoborohydride which is a solid-supported equivalent of tetraalkylammonium cyanoborohydride. The bound cyanoborohydride can be utilized as a versatile reducing agent for the reductive amination of carbonyl compounds and reduction of imines.Tags: Product Notes

Background

Biotage® MP-Cyanoborohydride is a macroporous polymer supported Cyanoborohydride, which is a solid-supported equivalent of tetraalkylammonium cyanoborohydride. The bound cyanoborohydride can be utilized as a versatile reducing agent for the reductive amination of carbonyl compounds and reduction of imines. Solid-supported cyanoborohydride can also be utilized for a number of other important reductive applications. Examples include reduction of a,b-unsaturated carbonyl compounds to the corresponding unsaturated alcohols, conversion of pyridinium ions to tetrahydropyridine derivatives, and dehalogenation reactions. The reaction work-up protocol is greatly simplified by using the solid supported reagent. Specifically, compared with the small molecule sodium cyanoborohydride, it is reported1 that toxic cyanide is not released on reaction workup and therefore does not contaminate the product or pose a danger towards the user.The general protocol for the use of MP-Cyanoborohydride for reductive amination is summarized as below

Reactions are performed with 2.5 equivalents of MP-Cyanoborohydride relative to the limiting reagent. The carbonyl compound is used as the limiting reagent in the synthesis of secondary amines to suppress over alkylation. For tertiary amine synthesis, the carbonyl compound is used in excess to allow the use of catch-and-release purification with MP-TsOH cartridges4 or SCX cartridges. The reactions are carried out with at least 5 equivalents of HOAc to facilitate formation of imine or iminium ions, which undergo reduction with MP-Cyanoborohydride. Tetrahydrofuran (THF) is preferred to dichloroethane as solvent due to its greater stability in the presence of reactive amines. After reduction is complete, the crude reaction mixture is comprised of the product amine as an acetate salt and excess amine or carbonyl compound depending on the stoichiometry employed. At this point, there are several options for final purification.

Representative Procedures

Reductive Alkylation of Primary Amines

To a 0.5 M THF solution of N-(3-aminopropyl)morpholine (1.2 mL, 0.60 mmol) was added 1.0 mL of a 0.5 M THF solution of cyclopentanone (0.50 mmol), 1.0 mL HOAc, and 1.0 mL THF. MP-Cyanoborohydride resin (0.5 g, 2.5 mmol/g, 1.25 mmol, 2.5 equivalents) was added and the reaction agitated at room temperature for 16 h. To the reaction mixture was added PS-Benzaldehyde (0.5 mmol) and the scavenging reaction mixture was stirred at room temperature for 16 h. The solution was filtered and the filtrate was concentrated to dryness. The crude product was dissolved in 2 mL of THF, and 0.89 g of MP-Carbonate (2.8 mmol/g, 2.5 mmol) was added. After 1.5 h the mixture was filtered and the filtrate was concentrated in vacuo to yield the desired secondary amine as a free base. The product secondary amine was characterized by gas chromatography and 1H NMRFor further information please see product note PPS392.

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Biotage is a global Life Science company that develops innovative and effective solutions for separation within organic and analytical chemistry, as well as for industrial applications. Biotage is listed on NASDAQ Stockholm.